Stress significantly impacts brain structure, particularly in the hippocampus, amygdala, and prefrontal cortex. The hippocampus has been central to understanding stress-related brain plasticity, including structural remodeling of neurons in response to acute and chronic stressors. Stress hormones like glucocorticoids and estrogens influence gene expression through both genomic and non-genomic mechanisms, with epigenetic changes playing a key role. These effects are modulated by other factors, such as excitatory amino acids (EAAs), and can lead to sex differences in outcomes. Chronic stress causes dendritic reorganization in the hippocampus, including shrinkage of dendrites in CA3 and dentate gyrus neurons, and loss of spines in CA1 neurons. This is accompanied by changes in neurogenesis and synaptic density, which can be influenced by factors like tPA and CRF. Stress also affects the amygdala, where dendritic expansion occurs in the basolateral amygdala (BLA) and spine density is reduced in the medial amygdala. These changes are linked to anxiety and memory impairments. The hippocampus is also involved in mood disorders and age-related memory loss. Stress can reduce hippocampal neurogenesis, while physical activity and enriched environments promote it. Epigenetic mechanisms, such as DNA methylation, play a role in stress-induced changes in glucocorticoid receptor (GR) expression and function. Early-life experiences, such as maternal care, can influence these epigenetic changes, affecting stress responses and mental health. Recent studies have identified rapid-acting antidepressants, such as ketamine and acetyl-L-carnitine (LAC), which act through epigenetic mechanisms. These drugs can quickly alter gene expression and synaptic plasticity, offering new treatment options for mood disorders. The hippocampus is also involved in the translation of animal model findings to human studies, showing effects of stress on brain structure and function in conditions like depression, PTSD, and Cushing's disease. Overall, stress has complex effects on brain structure and function, with both protective and damaging roles depending on the duration and intensity of the stressor. Understanding these mechanisms is crucial for developing effective treatments for stress-related disorders.Stress significantly impacts brain structure, particularly in the hippocampus, amygdala, and prefrontal cortex. The hippocampus has been central to understanding stress-related brain plasticity, including structural remodeling of neurons in response to acute and chronic stressors. Stress hormones like glucocorticoids and estrogens influence gene expression through both genomic and non-genomic mechanisms, with epigenetic changes playing a key role. These effects are modulated by other factors, such as excitatory amino acids (EAAs), and can lead to sex differences in outcomes. Chronic stress causes dendritic reorganization in the hippocampus, including shrinkage of dendrites in CA3 and dentate gyrus neurons, and loss of spines in CA1 neurons. This is accompanied by changes in neurogenesis and synaptic density, which can be influenced by factors like tPA and CRF. Stress also affects the amygdala, where dendritic expansion occurs in the basolateral amygdala (BLA) and spine density is reduced in the medial amygdala. These changes are linked to anxiety and memory impairments. The hippocampus is also involved in mood disorders and age-related memory loss. Stress can reduce hippocampal neurogenesis, while physical activity and enriched environments promote it. Epigenetic mechanisms, such as DNA methylation, play a role in stress-induced changes in glucocorticoid receptor (GR) expression and function. Early-life experiences, such as maternal care, can influence these epigenetic changes, affecting stress responses and mental health. Recent studies have identified rapid-acting antidepressants, such as ketamine and acetyl-L-carnitine (LAC), which act through epigenetic mechanisms. These drugs can quickly alter gene expression and synaptic plasticity, offering new treatment options for mood disorders. The hippocampus is also involved in the translation of animal model findings to human studies, showing effects of stress on brain structure and function in conditions like depression, PTSD, and Cushing's disease. Overall, stress has complex effects on brain structure and function, with both protective and damaging roles depending on the duration and intensity of the stressor. Understanding these mechanisms is crucial for developing effective treatments for stress-related disorders.